Bacterial cell wall composition and the influence of antibiotics by cell-wall and whole-cell NMR

Abstract

One contribution of 12 to a theme issue 'The bacterial cell envelope'. The ability to characterize bacterial cell-wall composition and structure is crucial to understanding the function of the bacterial cell wall, determining drug modes of action and developing new-generation therapeutics. Solid-state NMR has emerged as a powerful tool to quantify chemical composition and to map cell-wall architecture in bacteria and plants, even in the context of unperturbed intact whole cells. In this review, we discuss solid-state NMR approaches to define peptidoglycan composition and to characterize the modes of action of old and new antibiotics, focusing on examples in Staphylococcus aureus. We provide perspectives regarding the selected NMR strategies as we describe the exciting and still-developing cell-wall and whole-cell NMR toolkit. We also discuss specific discoveries regarding the modes of action of vancomycin analogues, including oritavancin, and briefly address the reconsideration of the killing action of b-lactam antibiotics. In such chemical genetics approaches, there is still much to be learned from perturbations enacted by cell-wall assembly inhibitors, and solid-state NMR approaches are poised to address questions of cell-wall composition and assembly in S. aureus and other organisms.

Structural Features Essential to the Antimicrobial Functions of Human SPLUNC1

“…Indeed, we found that inclusion of just six amino acid changes (D1 SPLUNC1) was sufficient to impart antibiofilm activity toward the Gram-positive pathogen S. aureus , albeit via an enigmatic mechanism given the anionic character of the S. aureus cell envelop. 40 Still, these results highlight the importance of this α1-α4 region in the antibiofilm activity of SPLUNC1, at least toward Gram-positive microbes, and suggest that additional protein variants may be created that further improve their effects against S. aureus and other bacterial pathogens.…”

Antimicrobial activity of species Zingiber officinale Roscoe and Alpinia purpurata (Vieill.) K. Schum. (Zingiberaceae) - Review

“…The extracts were more effective against gram-positive than gram-negative bacteria as reported by Kaushik and Goyal (2011). The higher resistance of gram-negative bacteria could be due to the complexity of the cell wall (ROMANIUK; CEGELSKI, 2015;SILHAVY et al, 2010;TEJADA et al, 2013).…”

“…The outer layer of gram-negative bacteria may be the primary mechanism underlying antibiotic resistance, as it is selective impermeable (DENYER; MAILLARD, 2002;ROMANIUK;CEGELSKI, 2015;SILHAVY et al, 2010;TEJADA et al, 2013).…”

NMR of Macromolecular Assemblies and Machines at 1 GHz and Beyond: New Transformative Opportunities for Molecular Structural Biology

“…Lippens and co-workers presented a method for combined J- and CP-based correlation with 13 CO detection at 900 MHz for characterization of disordered α-synculein in E. coli cells (102). Whole cell solid-state NMR studies have covered a wide range of systems including bacteria and biofilms to address many significant questions including perturbations in bacterial cell walls induced by drug binding (180, 181), cellular composition (182) and metabolomics (183), as well as monitoring of protein expression and cellular processes (184–186). These studies are essential to address pressing issues such as antibiotic resistance (187–189).…”